The long-term goal of this project is to develop a quantitative analysis of circulatory dynamics and their control. Therefore, our research program has been very broad, covering most aspects of the cardiovascular system and related control mechanisms. Two unique features of this program are that: (1) it extensively utilizes mathematical systems analyses in conjunction with animal experimentation to understand complex interactions between multiple components of the cardiovascular control systems and (2) it focuses on long-term as well as short-term control of the circulation because many cardiovascular diseases, such as hypertension and heart failure, are manifestations of abnormal control mechanisms that take place over long periods of time. The research proposed in this application is described by the titles of the specific projects, as follows: I. Computer Analysis of Circulatory Mechanisms II. Renal Control of Body Fluid Volumes and Circulatory Dynamics III. Neurohumoral and Renal Mechanisms of Hypertension IV. Hemodynamics and Endothelial Mechanisms V. Nervous System Mechanisms in Circulatory Control VI. Control of Microcirculatory Structure and Function The first project addresses the quantitative methodology for integrating all aspects of cardiovascular dynamics and circulatory control. The remaining projects address multiple interrelated areas of animal experimentation on mechanisms that influence cardiovascular dynamics, especially the kidneys, hormonal systems, the nervous system and local control mechanisms. These projects utilize a multidisciplinary approach, ranging from molecular and cellular studies to long-term studies in conscious animals. However, a common feature of all projects is that they focus on the integrative relationships between the circulation and other control mechanisms.